Osteoporosis is a major public health threat. National Osteoporosis Foundation estimated that the US national direct expenditures for osteoporotic hip fractures were at $17 billion in 2005 and it would increase to $25 billion in 2025. Current treatments for osteoporosis include several anti-resorptive (or anti-catabolic) and some anabolic agents. VDRMs such as calcitriol are currently used to treat osteoporosis in several ex-US countries. VDRMs influence bone metabolism through regulation of intestinal calcium absorption, parathyroid hormone, receptor activator of nuclear factor-kB ligand, and also via direct effects on osteoblasts and osteoclasts. Despite encouraging data on VDRM's benefits for treating osteoporosis, VDRMs are not used in osteoporosis patients in the US likely due to the fact that those currently on the market have substantial hypercalcemic toxicity that interferes with calcium homeostasis. All VDRMs on the market for osteoporosis are hypercalcemic, and require frequent serum calcium monitoring and dose titration. An ideal VDRM should be with little or no hypercalcemic toxicity in the efficacious dose range. Since VDRMs are well known to have anabolic effects on the bone, a VDRM without hypercalcemic toxicity for the treatment of osteoporosis will provide significant benefits to patients receiving the standard of care. Vidasym has taken a unique approach to discover and develop novel VDRMs. Data from extensive animal studies show that VS-105 has an exceptionally wide therapeutic index (TI) at >50-fold (comparing efficacy vs. side effect). We hypothesize that VS-105 will exhibit better efficacy than calcitriol in stimulating anabolic bone formation and also in increasing bone mineral density (BMD) with less hypercalcemic side effects. The specific aims of this Phase I study are: (1) To compare the effects between VS-105 and calcitriol on BMD and bone parameters in ovariectomized female rats. (2) To compare the effects between VS-105 and calcitriol on bone resorption and formation in mouse calvariae bone primary organ culture. Once this phase I study is completed, the data will allow the advancement of VS-105 into Phase II IND-enabling studies including VS-105 synthesis scale-up, process development and pharmacokinetics, metabolism, safety and toxicology. The completion of Phase II studies will allow VS-105 to enter human clinical trials. Vidasym plans to develop VS-105 into a reimbursable prescription drug to treat osteoporosis in patients receiving the standard of care. Based on the information provided by EvaluatePharma, osteoporosis medications achieved US$13+ billion in annual worldwide sales in 2011. This number is likely to increase based on the projections of increased patient numbers. The approach of developing VS-105 for osteoporosis, once introduced into the market, will decrease the incidence of vertebral fractures by at least 25 % (based on information from current on-the-market VDRMs for osteoporosis), which shall translate into ~$4 billion in annual health care savings in the US. Assuming Vidasym's VS-105 has a modest 5% penetration into the osteoporosis market, the estimated annual sales will be US$0.6+ billion.